Apoptosis and morphologic changes in drug-treated trabecular meshwork cells in vitro
Apoptosis and morphologic changes in drug-treated trabecular meshwork cells in vitro
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DOI：
10.1006/exer.1997.0458
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发表时间：
1998-05-01
影响因子：
3.4
通讯作者：
White, K
中科院分区：
文献类型：
--
作者：
Sibayan, SAB;Latina, MA;White, K
使用体外培养系统，我们研究了牛小梁网细胞在暴露于抗青光眼药物（噻吗洛尔、毛果芸香碱和肾上腺素）和已知的细胞凋亡诱导剂（5-氟尿嘧啶、丝裂霉素-C和地塞米松）后是否会发生细胞凋亡（程序性细胞死亡）。将第三至第五代牛小梁网细胞生长至汇合并在含有噻吗洛尔(1-1000μM)、毛果芸香碱(15-15000μM)、肾上腺素(5-5000μM)、5-氟尿嘧啶(10-100μgml(-1))、丝裂霉素-C(0.01-100μg)的生长培养基中培养1-12天。 ml(-1))和地塞米松(0.01-100μM)。通过相差显微镜、透射电子显微镜和原位细胞凋亡标记评估培养物的细胞凋亡。 5-氟尿嘧啶(10-100μgml(-1))、丝裂霉素-C(0.1-100μgml-1)和肾上腺素(500-5000μM)以剂量和时间依赖性方式诱导细胞凋亡。噻吗洛尔、毛果芸香碱和地塞米松处理的标本在任何测试浓度下均未显示细胞凋亡的证据。在噻吗洛尔（100-1000μM）中孵育的小梁网细胞产生细胞质颗粒，用毛果芸香碱（15000μM）处理的样本产生细胞质空泡。这些颗粒和液泡具有次级溶酶体的外观。地塞米松处理的细胞线粒体数量增加。这项研究表明，暴露于 5-氟尿嘧啶、丝裂霉素-C 和肾上腺素后，小梁网可能会发生细胞凋亡。噻吗洛尔、毛果芸香碱和地塞米松不诱导细胞凋亡。然而，这些药物可以引起培养的小梁网细胞的特征性形态变化。 (C) 1998 学术出版社有限公司。
Using an in vitro culture system, we investigated whether bovine trabecuIar meshwork cells undergo apoptosis (programmed cell death) following exposure to anti-glaucoma medications (timolol, pilocarpine and epinephrine) and known inducers of apoptosis (5-fluorouracil, mitomycin-C and dexamethasone). Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1-12 days in growth media with timolol (1-1000 mu M), pilocarpine (15-15000 mu M), epinephrine (5-5000 mu M), 5-fluorouracil (10-100 mu g ml(-1)), mitomycin-C (0.01-100 mu g ml(-1)) and dexamethasone (0.01-100 mu M). The cultures were evaluated for apoptosis by phase-contrast microscopy, transmission electron microscopy and in situ apoptosis labeling. 5-Fluorouracil (10-100 mu g ml(-1)), mitomycin-C (0.1-100 mu g ml-l) and epinephrine (500-5000 mu M) induced apoptosis in a dose and time-dependent manner. Timolol, pilocarpine, and dexamethasone-treated specimens did not show evidence of apoptosis at any of the concentrations tested. Trabecular meshwork cells incubated in timolol (100-1000 mu M) developed cytoplasmic granules, and specimens treated with pilocarpine (15000 mu M) developed cytoplasmic vacuoles. These granules and vacuoles have the appearance of secondary lysosomes. Dexamethasone-treated cells developed an increased number of mitochondria. This study suggests that the trabecular meshwork may undergo apoptosis following exposure to 5-fluorouracil, mitomycin-C and epinephrine. Timolol, pilocarpine and dexamethasone did not induce apoptosis. However, these drugs can incite characteristic morphologic changes in cultured trabecular meshwork cells. (C) 1998 Academic Press Limited.